WO2016088100A1 - Procédés pour préparer un phosphate de tédizolid et ses intermédiaires - Google Patents

Procédés pour préparer un phosphate de tédizolid et ses intermédiaires Download PDF

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WO2016088100A1
WO2016088100A1 PCT/IB2015/059374 IB2015059374W WO2016088100A1 WO 2016088100 A1 WO2016088100 A1 WO 2016088100A1 IB 2015059374 W IB2015059374 W IB 2015059374W WO 2016088100 A1 WO2016088100 A1 WO 2016088100A1
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formula
compound
process according
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tert
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Rakesh Singh
Atul Sharma
Mahavir Singh Khanna
Mohan Prasad
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Sun Pharmaceutical Industries Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

Definitions

  • the present invention provides processes for the preparation of tedizolid phosphate.
  • the present invention further provides compounds of Formula VIII, Formula IX, and Formula XI, processes for their preparation, and their use for the preparation of tedizolid phosphate.
  • Tedizolid phosphate chemically [(5i?)-3- ⁇ 3-fluoro-4-[6-(2-methyl-2H-tetrazol-5- yl)pyridin-3-yl]phenyl ⁇ -2-oxooxazolidin-5-yl]methyl hydrogen phosphate, is represented by Formula I.
  • Tedizolid phosphate is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria.
  • U.S. Patent No. 8,426,389 discloses a crystalline form of tedizolid phosphate.
  • the present invention provides processes for the preparation of tedizolid phosphate.
  • the present invention further provides compounds of Formula VIII, Formula IX, and Formula XI, processes for their preparation, and their use for the preparation of tedizolid phosphate.
  • ambient temperature refers to a temperature in the range of about 20°C to about 25 °C.
  • halogen refers to chloro, bromo, or iodo.
  • Ci-6 alkyl refers to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, tert-pentyl, neo-pentyl, iso-pentyl, sec- pentyl, 3-pentyl, n-hexyl, iso-hexyl, 2,3-dimethylbutyl, or neo-hexyl.
  • aryl refers to a monocyclic aromatic hydrocarbon.
  • An example of an aryl is phenyl.
  • aralkyl refers to a methylene substituted aryl group.
  • An example of an aralkyl is benzyl.
  • heterocycle refers to a non-aromatic ring containing one or more hetero atoms selected from the group consisting of oxygen (O), and boron (B).
  • O oxygen
  • B boron
  • An example of a heterocyclic ring is 4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl.
  • a first aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I,
  • Ri is Ci-6 alkyl
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • R 2 and R 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R 3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • a second aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I.
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • R 2 and R 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • a third aspect of the present invention provides a process for the preparation of a compound of Formula VIII,
  • Pi is a protecting group selected from the group consisting of tert-butoxy carbonyl, benzyloxycarbonyl, and benzyl,
  • a fourth aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I,
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • a fifth aspect of the present invention provides a process for the preparation of a compound of Formula IX,
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • P2 and P3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl, comprising reacting a compound of Formula VIII
  • R 2 and R3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6- membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • a sixth aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I,
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl,
  • R 2 and R 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R 3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • a seventh aspect of the present invention provides a process for the preparation of a compound of Formula XI,
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl,
  • R 2 and R 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R 3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6- membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • An eighth aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I,
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • P 2 and P 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl,
  • a ninth aspect of the present invention provides a process for the preparation of a compound of Formula XII,
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl,
  • a tenth aspect of the present invention provides a process for the preparation of tedizolid phosphate of Formula I,
  • Pi is a protecting group selected from the group consisting of tert- butoxycarbonyl, benzyloxycarbonyl, and benzyl,
  • An eleventh aspect of the present invention provides a compound of Formula VIII
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl.
  • a twelfth aspect of the present invention provides a compound of Formula IX
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • P2 and P3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl.
  • a thirteenth aspect of the present invention provides a compound of Formula XI
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl.
  • a fourteenth aspect of the present invention provides use of a compound of
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl, for the preparation of tedizolid phosphate of Formula I.
  • a fifteenth aspect of the present invention provides use of a compound of Formula
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl;
  • P 2 and P 3 each independently are Ci-6 alkyl, aryl, or aralkyl, or R 2 and R3 are taken together with the oxygen atoms to which they are attached to form a 5- or 6-membered heterocyclic ring, which is optionally substituted with Ci-6 alkyl, aryl, or aralkyl, for the preparation of tedizolid phosphate of Formula I.
  • a sixteenth aspect of the present invention provides use of a compound of Formula
  • Pi is a protecting group selected from the group consisting of tert-butoxycarbonyl, benzyloxycarbonyl, and benzyl, for the preparation of tedizolid phosphate of Formula I.
  • the compound of Formula II is reacted with the compound of Formula III to obtain the compound of Formula IV in the presence of a base and a solvent.
  • the base is selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, N,N-dimethylaniline, and pyridine.
  • the solvent is selected from the group consisting of ethers, hydrocarbons, halogenated hydrocarbons, N,N-dimethylformamide, acetonitrile, and mixtures thereof.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • hydrocarbons examples include n-hexane, n-heptane, cyclohexane, toluene, and xylene.
  • halogenated hydrocarbons examples include dichloromethane, chloroform, and 1 ,2-dichloroethane .
  • reaction of the compound of Formula II with the compound of Formula III is carried out for about 15 minutes to about 8 hours, for example, for about 30 minutes to about 4 hours.
  • reaction of the compound of Formula II with the compound of Formula III is carried out at a temperature of about 15°C to about 60°C, for example, of about 25°C to about 35°C.
  • the compound of Formula IV may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula IV may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula IV is reacted with the compound of Formula V to obtain the compound of Formula VI in the presence of a base and a solvent.
  • An example of a base is n-butyl lithium.
  • the solvent is selected from the group consisting of ethers, halogenated hydrocarbons, ⁇ , ⁇ -dimethylformamide, N-methylpyrrolidone, and mixtures thereof.
  • ethers include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • halogenated hydrocarbons include dichloromethane, chloroform, and 1 ,2-dichloroethane .
  • reaction of the compound of Formula IV with the compound of Formula V is carried out for about 15 hours to about 25 hours, for example, for about 20 hours to about 22 hours.
  • reaction of the compound of Formula IV with the compound of Formula V is carried out at a temperature of about -78°C to about 40°C, for example, of about -65°C to about 30°C.
  • the compound of Formula VI may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula VI may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula VI is reacted with an iodinating agent to obtain the compound of Formula VII in the presence of an acid.
  • An example of an iodinating agent is N-iodosuccinimide.
  • An example of an acid is trifluoroacetic acid.
  • reaction of the compound of Formula VI with the iodinating agent is carried out for about 2 hours to about 8 hours, for example, for about 3 hours to about 6 hours.
  • reaction of the compound of Formula VI with the iodinating agent is carried out at a temperature of about 15°C to about 60°C, for example, of about 25°C to about 35°C.
  • the compound of Formula VII may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula VII may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula VII is protected with a protecting agent to obtain the compound of Formula VIII in the presence of a catalyst and a solvent.
  • the protecting agent is selected from the group consisting di-tert-butyl dicarbonate, benzyloxycarbonyl chloride, and benzyl bromide.
  • the solvent is selected from the group consisting of dimethylsulfoxide, N,N- dimethylformamide, ethers, hydrocarbons, halogenated hydrocarbons, and mixtures thereof.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • hydrocarbons examples include toluene and p-xylene.
  • halogenated hydrocarbons examples include dichloromethane, chloroform, and 1 ,2-dichloroethane .
  • An example of a catalyst is 4-(N,N-dimethylamino)pyridine.
  • the protection of the compound of Formula VII with the protecting agent is carried out for about 5 hours to about 12 hours, for example, for about 6 hours to about 8 hours.
  • the protection of the compound of Formula VII with the protecting agent is carried out at a temperature of about 20°C to about 70°C, for example, of about 25°C to about 55°C.
  • the compound of Formula VIII may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula VIII may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula VIII is reacted with the compound of Formula A to obtain the compound of Formula IX in the presence of a palladium catalyst, a base and a solvent.
  • a palladium catalyst is [ 1, 1'- bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex.
  • An example of a base is potassium acetate.
  • the solvent is selected from the group consisting of dimethylsulphoxide, acetonitrile, ⁇ , ⁇ -dimethylformamide, 1,4-dioxane, and tetrahydrofuran.
  • the reaction of the compound of Formula VIII with the compound of Formula A is carried out for about 15 minutes to about 6 hours, for example for about 30 minutes to about 4 hours.
  • reaction of the compound of Formula VIII with the compound of Formula A is carried out at a temperature of about 15°C to about 80°C, for example, of about 20°C to about 70°C.
  • the compound of Formula IX may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula IX may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula IX is coupled with the compound of Formula X to obtain the compound of Formula XI in the presence of a palladium catalyst, a base and a solvent.
  • the palladium catalyst is selected from the group consisting of
  • the base is selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate, triethyl amine, and N,N- diisopropylamine .
  • the solvent is selected from the group consisting of water, N,N- dimethylformamide, ethers, alcohols, hydrocarbons, and a mixture thereof.
  • ethers examples include 1,4-dioxane, diethyl ether, diisopropyl ether, and tetrahydrofuran.
  • alcohols examples include methanol, ethanol, n-propanol, isopropanol, n- butanol, isobutanol, and tert-butanol.
  • hydrocarbons examples include benzene, toluene, and p-xylene.
  • the coupling of the compound of Formula IX with the compound of Formula X is carried for about 15 minutes to about 7 hours, for example, for about 30 minutes to about 6 hours.
  • the reaction of the compound of Formula IX with the compound of Formula X is carried out at a temperature of about 25°C to about 100°C, for example, of about 30°C to about 80°C.
  • the compound of Formula XI may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula XI may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula XI is deprotected in the presence of a deprotecting agent to obtain the compound of Formula XII in a solvent.
  • the deprotecting agent is selected from the group consisting of trifluoroacetic acid and hydrochloric acid.
  • the solvent is selected from the group consisting of ketones, halogenated hydrocarbons, ethers, alcohols, and mixtures thereof.
  • ketones include acetone and methyl ethyl ketone.
  • halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • alcohols examples include methanol, ethanol, n-propanol, isopropanol, n- butanol, isobutanol, and tert-butanol.
  • the deprotection of the compound of Formula XI in the presence of the deprotecting agent is carried out for about 1 hour to about 7 hours, for example, for about 2 hours to about 4 hours.
  • the deprotection of the compound of Formula XI in the presence of the deprotecting agent is carried out at a temperature of about 15°C to about 60°C, for example, of about 25 °C to about 35°C.
  • the compound of Formula XII may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization.
  • the compound of Formula XII may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula XII is phosphorylated in the presence of a
  • phosphorylating agent is phosphorus oxy chloride.
  • An example of a base is triethyl amine.
  • the solvent is selected from the group consisting of ethers, halogenated hydrocarbons, and mixtures thereof.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
  • the phosphorylation of the compound of Formula XII in the presence of the phosphorylating agent is carried out for about 2 hours to about 10 hours, for example, for about 3 hours to about 6 hours.
  • the phosphorylation of the compound of Formula XII in the presence of the phosphorylating agent is carried out at a temperature of about -10°C to about 10°C, for example, of about -7°C to about 8°C.
  • Tedizolid phosphate of Formula I may be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, or recrystallization. Tedizolid phosphate of Formula I may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the compound of Formula XII is phosphorylated to obtain tedizolid phosphate of Formula I by:
  • An example of the catalyst used in step a) is tetrazole.
  • the oxidizing agent in step a) is selected from the group consisting of hydrogen peroxide and m-chloroperbenzoic acid.
  • the solvent in step a) is selected from the group consisting of ethers, halogenated hydrocarbons, alcohols, and mixtures thereof.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
  • alcohols examples include methanol, ethanol, n-propanol, isopropanol, n- butanol, isobutanol, and tert-butanol.
  • reaction of the compound of Formula XII with di-tert-butyl N,N- diisopropylphosphoramidite in the presence of a catalyst in step a) is carried out for about 1 hour to about 30 hours, for example, for about 2 hours to about 10 hours.
  • reaction of the compound of Formula XII with di-tert-butyl N,N- diisopropylphosphoramidite in the presence of a catalyst in step a) is carried out at a temperature of about -70°C to about 10°C, for example, of about -65°C to about 5°C.
  • the compound of Formula B may optionally be isolated by employing one or more techniques selected from the group consisting of filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization.
  • the compound of Formula B may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • An example of the acid used in step b) is trifluoroacetic acid.
  • the solvent in step b) is selected from the group consisting of ethers, halogenated hydrocarbons, alcohols, and mixtures thereof.
  • ethers examples include diethyl ether, 1,4-dioxane, and tetrahydrofuran.
  • halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
  • alcohols examples include methanol, ethanol, n-propanol, isopropanol, n- butanol, isobutanol, and tert-butanol.
  • the deprotection of the compound of Formula B in the presence of an acid is carried out for about 30 minutes to about 3 hours, for example, for about 45 minutes to about 2 hours.
  • the deprotection of the compound of Formula B in the presence of an acid is carried out at a temperature of about 15°C to about 60°C, for example, of about 25°C to about 35°C.
  • Tedizolid phosphate of Formula I may be isolated by employing one or more techniques selected from the group consisting of filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization. Tedizolid phosphate of Formula I may further be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, freeze drying, air drying, or agitated thin film drying.
  • the NMR spectrum was recorded using a Bruker ® Avance III (400 MHz) NMR spectrometer.
  • the Mass spectrum was recorded using a MASS (API2000) LC/MS-MS system, Q Trap ® LC/MS-MS system (Applied Biosystems ® ). The chromatographic purity was recorded using an Acquity ® H-class UPLC, PDA Detector.
  • Methyl (3-fluorophenyl)carbamate (Formula IV, 70 g, Example 1) was dissolved in anhydrous tetrahydrofuran (420 mL) at ambient temperature and the solution was cooled to -65°C to -60°C under nitrogen atmosphere.
  • n-Butyl lithium (1.6 M in hexane, 272 mL) was slowly added to the above solution under a nitrogen atmosphere, and then the reaction mixture was stirred for 10 minutes.
  • reaction mixture was warmed to ambient temperature, and then stirred for 20 hours at 20°C to 25 °C under nitrogen atmosphere. After completion of the reaction, ammonium chloride solution (7 g dissolved in 70 mL of deionized water) was added to the reaction mixture.
  • Tetrahydrofuran was recovered under vacuum at 40°C to 45 °C, followed by the addition of deionized water (500 mL) at 40°C to 45°C. The reaction mixture was allowed to attain ambient temperature and was then stirred for 2 hours. The solid obtained was filtered, then washed with deionized water (70 mL). The wet solid was dried at 50°C to 55°C to afford the title compound.
  • Deionized water 50 mL was added to the residue, followed by the addition of ethyl acetate in hexanes (20%, 30 mL). The resulting biphasic system was stirred at ambient temperature for 15 minutes, then cooled to 0°C to 5°C, and then stirred for another 1 hour at 0°C to 5°C. The solid obtained was filtered, then washed with deionized water (40 mL) and 20% ethyl acetate in hexanes (30 mL). The solid was dried at 40°C to 45°C for 4 hours to afford the title compound as an off-white solid.
  • the solid obtained was filtered, then washed with cold methanol (3 x 25 mL). The solid was dried at 45 °C for 6 hours to 7 hours to afford a crude compound (4.4 g).
  • the crude compound (4.2 g) was dissolved in methanol: dichloromethane (1 : 1, 350 mL) at ambient temperature.
  • Activated carbon (1 g) was added, then the solution was stirred at ambient temperature for 1 hour.
  • the solution was filtered through a Hyflo ® , and then the bed was washed with methanol: dichloromethane (1 : 1, 50 mL). The mother liquor was concentrated under vacuum to dryness.
  • Tetrahydrofuran 75 mL was added to (5R)-3- ⁇ 3-fluoro-4-[6-(2-methyl-2H- tetrazol-5 -yl)pyridin-3 -yl]phenyl ⁇ -5 -(hydroxymethyl)- 1 ,3 -oxazolidin-2-one (Formula XII, 3 g, Example 7) while stirring under an inert atmosphere.
  • the reaction mixture was cooled to -5°C in an ice bath, then triethylamine (3.4 mL) was added to the mixture.
  • Phosphorous oxy chloride 2.3 mL was added to the reaction mixture at -5°C to 0°C over 10 minutes to 15 minutes.
  • the reaction mixture was stirred at 0°C to 5°C for 4 hours to 5 hours.
  • the reaction mixture was slowly poured into another flask containing deionized water (110 mL) precooled to 0°C to 5°C. The temperature was maintained below 10°C during addition.
  • the yellow slurry thus obtained was stirred overnight at ambient temperature.
  • the solid obtained was filtered, then washed with deionized water (15 mL) and methanol (30 mL). The solid was dried at 45°C for 6 hours to afford the title compound.
  • reaction mixture was cooled to -70°C to -65°C followed by the addition of m- chloroperbenzoic acid (0.7 g).
  • the reaction mixture was stirred for 2 hours at -70°C to - 65°C.
  • the reaction mixture was warmed to ambient temperature.
  • Dichloromethane (20 mL) and an aqueous solution of sodium bisulfate (0.5 g dissolved in 20 mL deionized water) were added to the mixture.
  • the organic layer was separated, then washed with an aqueous solution of sodium bicarbonate (0.5 g dissolved in 20 mL deionized water), followed by deionized water (20 mL).

Abstract

L'invention concerne des procédés de préparation de phosphate de tédizolid. L'invention concerne également des composés représentés par la formule (VIII), la formule (IX) et la formule (XI), leurs procédés de préparation et leur utilisation pour préparer un phosphate de tédizolid. Les procédés de l'invention utilisent des réactifs non-toxiques et bon marché, sont industriellement viables, et permettent de produire un phosphate de tédizolid présentant une pureté et un rendement élevés.
PCT/IB2015/059374 2014-12-05 2015-12-04 Procédés pour préparer un phosphate de tédizolid et ses intermédiaires WO2016088100A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11555033B2 (en) 2020-06-18 2023-01-17 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090192197A1 (en) * 2003-12-18 2009-07-30 Dong-A Pharm. Co., Ltd. Novel oxazolidinone derivatives
US20100093669A1 (en) * 2008-10-10 2010-04-15 Trius Therapeutics Methods for preparing oxazolidinones and compositions containing them
US20100227839A1 (en) * 2009-02-03 2010-09-09 Trius Therapeutics Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin- 5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090192197A1 (en) * 2003-12-18 2009-07-30 Dong-A Pharm. Co., Ltd. Novel oxazolidinone derivatives
US20100093669A1 (en) * 2008-10-10 2010-04-15 Trius Therapeutics Methods for preparing oxazolidinones and compositions containing them
US20100227839A1 (en) * 2009-02-03 2010-09-09 Trius Therapeutics Crystalline form of r)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin- 5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11555033B2 (en) 2020-06-18 2023-01-17 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof
US11566023B2 (en) 2020-06-18 2023-01-31 Akagera Medicines, Inc. Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof

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